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I'm not knowledgeable enough to know if there are cases of people that have been "undetectable" for more than 10 years without meds. If this is the case, then I would think that they managed to kick out the virus for good and this is a great thing. They will be test hiv+ because they have antibodies, but they're out of it, and possibly completely immune. I'm new to this so I don't know if we've seen such cases yet.

What I find interesting is people that have a viral load of 100000+ then drop to undetectable to 70 to 1000 to undetectable etc..

Those, from what I understand are affected by mutants that made it during the rna conversion and are hiding, or "maturing". They are weak, most will die because of darwin selection, but others will survive. The mutation test (i don't remember its name) is rarely disclosed, and I haven't seen it on people's reports here in those forums, but it could be an indicator as what's going on. Remember, the results we get are per cubic millimeter, so there are actually zillions of viruses in our body, not just 40, and the sample is taken from blood in the arm, not in the glands that may host mutants or hidden viruses.

The mutation is not on purpose, it's an "error" that happens during rna/dna conversion, but that error seems to confuse/give more work to CD4s, which are already weakened by the virus using them as a factory.

I like the new "entry drugs" because they work on disabling entry to the cell by either having the CD4 "ignore" the virus, which then just dies of boredom, or confuse the virus that thinks it got a good bind but then gets its entry protein wiped out and is unable to do anything.

I'm totally not an hiv specialist, the first time I learned about how all this works was few days ago, but i'm a fast learner and I'm very logical (this is the basis of my day job), and by applying logic after reading how the virus works I don't see how rna-dependent polymerase or other transcriptase meds can get the count of viruses to zero. I'm talking about a cure here, not an avoidance against OIs, so don't get me wrong, I DO believe that those existing drugs ARE working to keep us alive, but it's not a "cure".

I'm not knowledgeable enough to know if there are cases of people that have been "undetectable" for more than 10 years without meds. If this is the case, then I would think that they managed to kick out the virus for good and this is a great thing. They will be test hiv+ because they have antibodies, but they're out of it, and possibly completely immune. I'm new to this so I don't know if we've seen such cases yet.

Maybe i'm completely wrong, let me know.

You're completely wrong! At least on this point. Nobody has ever kicked out the virus for good. A small number of people who remain undetectable for long periods of time on HAART serorevert - i.e. they no longer have antibodies to HIV, and would test negative on an HIV antibody test. However, if you take away the HAART, viral load rebounds to whatever it would have been if HAART had never been taken. So you've got that part of it the wrong way round. That's why at the moment, once you're on therapy, you're on it for life.

The reason the VL rebounds is because of latency - pools of infected, but dormant, immune cells that persist for upto 60 years. Periodically the virus in them is activated, resulting in blips of activity. If no HAART were constantly present, the VL would quickly reinfect and destroy new CD4 cells.

The people you refer to who obtain undetectability without drugs are rare, and it's usually down to their genetics. The most common reason is an inherited deletion of del32, which results in less CCR5 receptors on CD4 cells, which are used as a common co-receptor by the virus to get into cells. Some of them may have a weaker strain, with less reproductive capacity.

Hence the new CCR5 inhibitor, maraviroc. The problem I have with drugs like this is that they modify the patients' immune systems, rather than anything specific to HIV. With CCR5 this is unlikely to be a problem, as there are people walking around with no CCR5 receptors at the moment as part of natural variation, but you have to wonder with other drugs coming down the pipeline.

You're right. HIV is what is known as a "sloppy copier". It's not great because it means that the genes in HIV are constantly being slightly altered. Certain classes of drugs, like the NNRTIs are very fragile and only a small mutation is needed for HIV to be resistant to the entire class of drugs. The development of more resistant drugs in the NNRTI class is beginning to bear fruit, such as TMC125 from Tibotec.

All in all, HIV is a fascinating virus, and certainly there are major advances in the pipeline. The question of cure is a pretty contoversial one - the twin problems of compartments (getting anti-HIV drugs into the brain/balls/other sites they don't penetrate that well) and latency, described above, both need to be overcome.

Matt, this is exactely what i'm saying, and that you confirm what I wasn't sure: there are no cases of undetectable people that stay like this for 10 years or more with meds. What I was saying was "IF there were such cases"!

As for seroreversion, the only thing I could find is studies from 1996 and 1999 and stuff about infants that are hiv at birth then serorevert later, but nothing else, which make me think that at that time the tests were not sensitive enough? Do you have anything about this, I couldn't find anything on here either.

I think we're saying the same thing, at least what you say is exactely what I was trying to say

HIV DART 2006 focused on 'Frontiers in Drug Development for Antiretroviral Therapies' and assembled clinicians, researchers, scientists and pharmaceutical company representatives from around the world. Biotron presented preclinical data showing the antiviral effect of BIT225 in macrophage cells.

These cells are one of the major reservoirs of HIV infection in humans, and current HIV treatments are not effective against HIV in these cells. In HIV-infected patients HIV hides in the reservoir cells, where it replicates and is released into the blood, where it infects CD4 T cells, setting up a continual cycle of infection and re-infection in the body. Biotron presented data demonstrating that BIT225 is able to prevent spread of virus between these reservoir cells and also stops transmission of HIV to CD4 T cells.

Biotron's presentation on BIT225 received an award at the meeting, demonstrating the high level of interest in its antiviral program. The award is also an acknowledgment of the robustness of the science underlying the company's programs.

BIT225 represents a novel, first in class approach to the treatment of HIV. BIT225 is specifically active in HIV reservoir cells and represents an opportunity to attack HIV at its source. As previously advised, the company is currently completing formal preclinical safety studies and preparing ethics and regulatory submissions for approval to commence human clinical trials early in 2007.

This article was prepared by Virus Weekly editors from staff and other reports. Copyright 2007, Virus Weekly via NewsRx.com.

Biotron’s lead compound hits HIV by a novel mechanism of action. BIT225,which goes to the clinic late in 2006, is the first of a potential new class of HIV drug.The clinical demand for new kinds of HIV drugs is strong. And BIT225’s apparentability to target ‘viral reservoirs’ hitherto out of reach of existing HIV drugs shouldmake it particularly attractive to potential licensing partners.Hepatitis C is an unmet clinical need. The science behind BIT225 has alsoenabled Biotron to identify some promising potential Hepatitis C drug candidates.Hepatitis C is a US$3bn market that is markedly underserved by the existing drugs.We expect that Biotron’s Hep C drug will go to the clinic in late 2007.

Biotron has completed a $4.6m capital raising. This will fundPhase I/IIa clinical trials for Biotron’s lead compound, the anti-HIV drug BIT225, as well as for an anti-Hepatitis C compound.Biotron’s Hep C programme, where a clinical candidate isexpected to be selected soon, has enormous upside given thecurrent state of the Hep C therapeutics marketWe expect strong partnering interest in both HIV and Hep CBiotron’s compounds have also shown potential against thedengue and SARS viruses. And at least one proprietarycompound has successfully targeted the H5N1 strain of bird flu

Why Biotron’s BIT225 drug is worth backing in HIV. Biotron has rationally designed a libraryof 200 novel compounds that are VPU inhibitors. The best of the best of these compounds,BIT225, is good at hitting HIV and it’s also:potentially a pill (68% of the drug gets into the bloodstream via the gut wall);possessed of good drug-like qualities in terms of safety, stability and half-life;effective against drug- resistant strains of HIV;easy to make and;‘synergistic’ with existing HIV drugs, boosting its chances of being favoured byclinicians.Why Biotron’s anti-Hepatitis C concept is worth backing. Biotron has obtained experimentalevidence that the scientific approach it has taken in HIV could also be used in Hepatitis C.Page 2 of 4Southern Cross EquitiesPage 3Biotron (BIT)A timeline for Biotron looking forwardBIT225Q2 ‘06 – Completion of production of BIT225 for trial purposesQ4 ’06 – Completion of formulation of BIT225 so that it can be injected into patients. Variousdossiers filed with the regulators and ethics committees ahead of BIT225’s first human trial.Q4 ’06 – Announcement of BIT225 Phase I/IIa (ie early stage) trial structure and commencementof dosingQ2 ’07 – Results of I/IIa trial announced

20 Bridge StreetSydney NSW 2000(2 pages by email)Dear MadamMANUFACTURE OF BIOTRON'S ANTI-HIV DRUG BIT225The Directors of Biotron Limited ('Biotron' or 'the Company') are pleased to advise thatcommercial manufacture the Company’s lead anti-HIV drug, BIT225, is on schedule with themanufacturing of the first of two 2.5 kilogram batches of GMP-grade BIT225 having beencompleted.As previously advised, Dr Reddy’s Laboratories Ltd, Hyderabad, India was contracted tomanufacture and supply 5 kilograms of GMP-grade BIT225.The commercial GMPmanufacturing process was divided into two 2.5 kilogram batches to minimise any risk associatedwith the manufacturing process and to validate the process. The contract included processdevelopment and scale up of the manufacturing process from the previous bench top scale to largescale reactors. Process development and scale up was completed prior to manufacture of the first2.5 kilogram batch and manufacture of the second batch of BIT225 is underway.Excellent results have been achieved in terms of product quality, and have demonstrated thatBIT225 may be successfully scaled up from lab to commercial scale. The manufacturing is beingdone to audited international regulatory standards and will be suitable for use in human clinicaltrials.In parallel with the manufacture of GMP-grade BIT225, preclinical safety studies are in progresswith a European contract research organisation. These studies include longer-term, chronic,multiple-dosing toxicity tests in two species of animals, as well as additional in vitro safety tests.The Directors are pleased with the progress of these studies and results to date have beenconsistent with preliminary safety studies undertaken during the lead compound selectionprogress. The data from these studies and the preliminary safety studies will be submitted toappropriate hospital, ethics and regulatory authorities to support approval for commencement of aPhase I/IIa human clinical trial for HIV.Page 22BIT225 represents a novel, first in class approach to the treatment of HIV. BIT225 has a newmode of action against HIV compared to existing anti-HIV therapies, targeting the Vpu protein ofHIV. By blocking a new pathway in HIV infectivity, Biotron’s Vpu inhibitors have the potentialto combat drug-resistant viral strains, in combination with highly active antiretroviral therapies('HAART') and in monotherapy. Unlike existing drugs, BIT225 is active in the viral reservoir inthe body, and complete elimination of HIV from infected patients is not possible unless theseunderlying reservoirs of infection can be cleared. BIT225 represents an opportunity to eliminatethe underlying seat of infection, potentially leading to a cure for HIV.In summary, commercial GMP scale-up and manufacture of BIT225 as well as the formalpreclinical safety studies are on track for completion this calendar year. Biotron is finalising thesite and design of the proposed Phase I/IIA human clinical trial.For further information, please contact Dr. Michelle Miller, CEO, on (61-2) 61258001.Yours sincerelyPeter J. Nightingale

Received 3 November 2003/ Returned for modification 6 January 2004/ Accepted 20 February 2004

We report that the amiloride analogues 5-(N,N-hexamethylene)amiloride and 5-(N,N-dimethyl)amiloride inhibit, at micromolar concentrations, the replication of human immunodeficiency virus type 1 (HIV-1) in cultured human blood monocyte-derived macrophages. These compounds also inhibit the in vitro activities of the HIV-1 Vpu protein and might represent lead compounds for a new class of anti-HIV-1 drugs.

This is not going to be a cure. It's another possible HIV drug. Lots of drugs fail at Phase I/II clinical trials, so this one is not blowing my skirt up yet. The other thing is that macrophages are only one of the cell types used as viral reservoirs.

How about telling us what you think, rather than cutting and pasting huge posts? There's tons of this stuff on the internet, I read it too - but I don't consider the bulk of it worth posting. What, in your opinion, makes this drug special?

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ROCHESTER, Minn. -- Mayo Clinic researchers have identified a way to manipulate the body’s own natural killer cells to destroy cells containing the HIV virus. Current treatments for HIV block the virus from replicating, but don’t kill the cells that contain HIV. The existence of these HIV-harboring cells -- often called the “latent” or “resting reservoir” -- is regarded by many to be the main obstacle to finding a cure for HIV.

“These drugs used to treat patients today -- which do an excellent job on suppressing replicating virus -- do nothing for the infectious virus contained within the latent reservoir,” says Andrew Badley, M.D., the lead immunovirologist of the Mayo Clinic research team. “If we can find a way to kill the virus that is present within the latent reservoir, we are on to a promising path towards a cure for HIV.”

To address the latent reservoir problem, Dr. Badley’s team built upon their earlier findings that showed a molecule named TRAIL to be a potential agent for treating HIV within the resting reservoir. The experiment was performed on cells taken from HIV-infected patients and then treated in laboratory test tubes. Results showed the molecule was effective in killing the HIV cells in a majority of samples. While successful in test tubes, this approach is many years away from being tested on patients in clinical trials. The research findings appear today in the online edition of the June 11 issue of the Journal of Virology (http://jvi.asm.org).

Significance of the Mayo Clinic Research The “resting reservoir” refers to HIV virus particles within cells that have stopped replicating. Consequently, the HIV within these cells eludes current drug treatments because these drugs only work on actively replicating HIV. This allows the HIV to hide in a dormant or resting stage in certain cells. The resting reservoir serves as a kind of HIV time bomb that can detonate if a patient stops HIV treatment or becomes resistant to current drugs.

The TRAIL molecule TRAIL is a naturally-occurring molecule made by many cells of the immune system. For reasons that are as yet unclear, it possesses the ability to kill only abnormal cells, such as cancer cells or those containing HIV. It sends signals to prompt cell death in the abnormal cells, while leaving healthy cells alone.

This seek-and-destroy ability of TRAIL is also under investigation for the treatment of certain cancers, but the Mayo Clinic researchers are the first to publish results on TRAIL as a possible immunotherapeutic treatment for HIV infection and AIDS.

The Experiment The team set out to discover if TRAIL could work against human cells in a test tube and also if the body could be prompted to produce more TRAIL.

The researchers treated cells from HIV-infected patients with recombinant TRAIL, and in all cases, such treatments reduced the amount of virus present. “And in three out of five test tube samples, we were able to destroy all signs of HIV. Therefore TRAIL shows promise as a way of disabling the latent reservoir in the test tube,” Dr. Badley says.

To investigate the second point, the researchers investigated two compounds to see how they increase the function of natural killer cells both from HIV-infected patients, and from non-HIV-infected patients. Like many other immune system members, natural killer cells make TRAIL. Researchers wanted to find a way to induce them to produce more TRAIL. The two compounds they thought might be able to do that belong to the same family of Interleukins, specialized proteins which are widely known to be important players in the immune system for communicating messages. The research team compared the effectiveness of Interleukin-15 (IL-15) and Interleukin-7 (IL-7) at increasing the immune system’s ability to kill HIV infection. Results show that both enhance NK cell function, but that they work differently. Of the two, IL-15 increases the expression of TRAIL. “It therefore may be the more promising immunotherapeutic agent for HIV,” Dr. Badley says.

Currently neither TRAIL nor Interleukin-15 has been tested in patients. “We hope to pursue such work in the future. But in the here and now, I’d simply say we are very encouraged by our results,” says Dr. Badley.

Other authors of the study are, from Ottawa Health Research Institute, University of Ottawa: Julian J. Lum, Zilin Nie (also of Mayo Clinic), Jaime Sanchez-Dardon, Georgina L. Mbisa, Nanci Hawley, Shanil Narayan; from the National HIV/AIDS Laboratories, Health Canada: Jennifer Mihowich and John E. Kim; and from Immunex Corporation, Seattle: David H. Lynch.

Dr. Badley is supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation.

As thrilling as it is to read about "exciting new breakthroughs in HIV therapy" (words that I can recall having seen dozens of times since I began taking a casual interest in the subject in the late 1990s), it would seem that with the exception of new drugs, we're still working in the paradigm of HAART.

What works beautifully in a lab is often thrown into complete disarray when dealing with the complex system that is the human body.

Pharmokinetics, tolerability, safety, efficacy... there are any number of issues that could cause a drug to fail at the beginning of the pipeline... and many promising innovations in drug therapy for any number of diseases have had to be abandoned because the drugs that had previously been touted as "exciting breakthroughs" didn't work so well.

You don't hear a lot about those. Really, does anyone ever wonder why you don't hear too many follow-ups on these "new and exciting" announcements from labs?

But look up "TGN1412" in Google to see just one of the many things that can go wrong in a clinical trial.

Me, I don't get too excited about press releases and "promising laboratory indications." A hell of a lot of them go absolutely nowhere for hundreds of reasons.... like the drug they developed kills people.

Personally, I start paying serious attention around phase III.

And I only pop open a bottle of bubbly when the new drug appears on my insurance company formulary.

I didn't want to intervene before because I don't even take the drugs yet, but what aupoint said was my feeling. I've heard about "amazingly promising drugs" since 1985, and yes, some of them have been amazing, but so few. I agree, stage III is where is da shit that would start getting me excited (and I get excited by much less, usually, but you don't want to know).

I totally disagree with this statement, "Phase I/II trials are absolutely nothing... nothing to get excited over."

First to even get to phase I it takes an idea, a light bulb going off in a scientists mind, a researcher, after working for years and decades, and reading and learning and saying hey this new development over here leads me to this new idea. Then they try that idea on a few cells in a dish, wow they find that it works it is a big discovery, people win the nobel prize even at this level, then they do little mice trials probably have phases too, and wow they now have mice that have the disease so they have mice models, called murine models, mice with diabetes, mice with all types of human diseases, they try their new idea on the mice and many different dose levels, WOW they find that it works, wow its great, the find the best dose then, the know from experience that a mouse dose is 1mg and a human dose is 100 mg for example, then they try phase one two etc, different doses starting out at tiny tiny doses. anyway then if it works and not too many bad things, they go up to phase three which is just more people, so really by phase 2 alot is known and it is really a big big deal that it works in phase 2 it has already worked in 5 steps before that...

the other reason to be excitied is we are now past the tipping point of the virus, it use to be that they knew nothing about hiv and alot about cancer, now they know say 90% of hiv and everyday are finding new things

The writer i disagree with wrote, "But look up "TGN1412" in Google to see just one of the many things that can go wrong in a clinical trial." forget about the TGN1412, yes there was a small problem, but it was only because this new gene therapy stuff, genetic engineering and actually dna manipulation is very tricky, the tgn1412 thing was very simple... went like this... they found this perfect cool thing that worked in the dish, worked in the mouse, worked in the chip and monkey (oh i forgot that part above there are always monkey and chimp trials tests before phase one in human) anyway, the genetic therapy worked great in all these animals so they thought well we give 1mg to a mouse so lets try instead of 100 mg for a human, 1/500 of a milligram just to be sure, they give a super low dose to humans, and they did it at same time silly english people, but really it was a tiny tiny dose, so then some the volenteers had a bad reaction, because, hey the scientists made a huge discovery, the human body has like 1000 times more receptors for this gene therapy than a monkey or mouse, human system is much more complicated, big deal, it was dosing... of super new gene therapy... not the end of world, just from one silly dose issue do not throw out every phase 1 and phase 2 trial

also we are now in golden age of hiv research where all the hard deep science of 25 years and billions of dollars has finally paid off and they know 90% of what they need for cure

see my other posts on mostly research news

forget about that one thing... it was tiny blip, gene therapy itself is so so huge and gaigantic, it is like saying, a model T car caught on fire, autos will never work and zoom

new great advances that are going to win nobel prize and some have application to cancer as well as hiv

are being announced every week for the last 14 years, it is an exciting time in science

I don't think he was saying that unless phase III is reached it's shit. I think he was saying that unless level III is reached then this when we should get excited about. Level I and II studies are great but we've seen so many of them that failed and didn't reach level III I think this is what he was saying.

I used it to back up my point that many, many drugs have had to have been tossed aside because of unforeseen consequences in humans. With all our computers and knowledge, we still gotta test it in people. And more often than not those tests fail. Either, in the words of the Verve, the drugs won't work, or because they kill people, or because the side-effects are intolerable... or for dozens of other reasons.

How many "breakthroughs" have been heralded in the press over the past 25 years regarding HIV? I would be willing to bet it's somewhere in the hundreds, if not thousands.

How many drugs have been shown to really work on HIV? Not counting repackaged deals... it stands at about 30, I believe.

The road to treating this virus is riddled with a lot of dead people and a lot of failed treatment attempts.

I simply demand to see results that show what they've developed a) works, and b) won't kill my ass. I don't care how well it does in a test tube. Bleach kills HIV in a test tube, but they don't prescribe Clorox.

My point is simply this... it's perhaps not advisable to wet our collective pants with glee every time an alleged new breakthrough has been potentially seen in a test tube. There have been many disappointments, and there will be many more in the future.

They tried selling poz people on AZT monotherapy in the 1980s thinking it would do great things for them.

What happened?

A lot of people died. And a lot of people suffer from the toxicities today.

You're completely correct in that we know a great deal more about HIV than we did 20, 10, or even 5 years ago. And who's to say how much we'll know in 10 years time? But I would regard any statement about knowing "everything" about HIV with nothing but the highest skepticism.

90% isn't 100%, and I doubt we'll get there in the next several decades. They can't even predict the next year's flu strains accurately, for crying out loud.

This virus has shown itself time and time again to be an extraordinarily wily opponent.

Every time a new treatment option is used... HIV figures out a way around it.

Who would have thought that the damn thing would go into reservoirs in 1995 with the advent of protease inhibitors? Who would have thought that resistance to Viramune would equal resistance to every NNRTI currently available?

These problems only came up when a new treatment was made available... because of the nature of the virus we're fighting. Who's to say what this darling of natural selection will come up with with future treatment options?

The arrogance of and over-dependence in the infallibility of science is what got us into this mess in the first place. In the 1960s and 1970s, everyone thought that infectious diseases were on the wane, antibiotics and vaccinations had beaten smallpox, childhood diseases, and syphilis. Infectious disease ranked very low on the list of priorities at the time... simply because people had become too complacent in science's ability to solve all problems resulting from them.

Warning signs about a certain odd syndrome that seemed to result from immune system suppression were completely ignored... because hey, science had it all under control, and it couldn't possibly be a new virus, right?

Oops.

We were caught with our pants down (pardon the pun) because we thought we knew everything about infectious disease.

This is why I have a certain amount of distrust in thinking that every breakthrough heralds the end of HIV... they haven't yet twenty four years after identifying HIV... and I highly doubt that they anything will.

Gee, didn't you know? HIV was cured in the late 1990s. Read U.S. newspapers and magazines from the period! AIDS has dropped from the national focus and infections are rising again because many people know HIV infection is only a matter of taking a few pills every day for the rest of your life. Like aspirin for heart attacks.

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Life is full of pain, I'm cruisin' through my brainAnd I fill my nose with snow and go Rimbaud,Go Rimbaud, go Rimbaud,And go Johnny go, and do the watusi, oh do the watusi

Gee, didn't you know? HIV was cured in the late 1990s. Read U.S. newspapers and magazines from the period! AIDS has dropped from the national focus and infections are rising again because many people know HIV infection is only a matter of taking a few pills every day for the rest of your life. Like aspirin for heart attacks.

Warning signs about a certain odd syndrome that seemed to result from immune system suppression were completely ignored... because hey, science had it all under control, and it couldn't possibly be a new virus, right?

As U.S. citizens we cannot forget a "disease only gay men got" was ignored and research was stymied for years at the very highest level of our government, President Ronald Reagan. There were many scientists and doctors who recognized AIDS for what it is but funding was non-existent while Ronnie kept budgeting more and more for defense and slashing all other federally funded programs. It wasn't until Rock Hudson was outed as moribund with AIDS that the national press gave AIDS closer scrutiny and it was mostly sensationalist crap even then. Thousands of people died before Reagan even said the word AIDS in public.

Sorry to wander off-topic but it wasn't only scientific hubris which impeded the response to the pandemic, at least not in the USA.

Logged

Life is full of pain, I'm cruisin' through my brainAnd I fill my nose with snow and go Rimbaud,Go Rimbaud, go Rimbaud,And go Johnny go, and do the watusi, oh do the watusi

As U.S. citizens we cannot forget a "disease only gay men got" was ignored and research was stymied for years at the very highest level of our government, President Ronald Reagan. There were many scientists and doctors who recognized AIDS for what it is but funding was non-existent while Ronnie kept budgeting more and more for defense and slashing all other federally funded programs. It wasn't until Rock Hudson was outed as moribund with AIDS that the national press gave AIDS closer scrutiny and it was mostly sensationalist crap even then. Thousands of people died before Reagan even said the word AIDS in public.

Sorry to wander off-topic but it wasn't only scientific hubris which impeded the response to the pandemic, at least not in the USA.

You're right.

But that was in the 1980s... when it was already way too late. The response of the US government in the years after AIDS was first identified was criminal.

I'm referring to the warning signs that appeared in the preceding decades... first in the 1960s and then a bit more in the 1970s. They were ignored.

This is an interesting poll. I would consider those that visit these forums to be more up on the news of HIV treatment and potential for vaccines and cures. Does it amaze anyone else that 51 of 104 respondents say that they think HIV/AIDS will be cured in the near future? I voted yes but not in the next 10 years, call me conservative I guess.

I would consider those that visit these forums to be more up on the news of HIV treatment and potential for vaccines and cures.

I think you're right, but I think if you look at any group of people living with a disease, a lot of them will say the cure is just around the corner. I personally think that people need hope in order to deal with something like this - and that skews things. I also think a subset of people deny themselves any hope in order to make sure they're "dealing with reality". I think the reality is inbetween these two viewpoints.

The cure is obviously NOT around the corner with HIV - nobody is anywhere near doing a study (itself a 2/3/4-year endeavour) with an expected outcome being the eradication of HIV. We'll be lucky to see it in the next 10 years. But neither has it yet to be shown to be an insurmountable problem, although I've read studies that have opined it is, it is not the overall view. Yet. I think Benj raises an important point in terms of the politics of this - the reason nobody has ever thrown up their hands and called cancer unsolvable is because of the sheer political clout and widespread nature of it. We have to make sure that we're not marginalised ('gay man's disease') and that we continue to lobby.

Matt I respect your writing and think you have good things to say, but i disagree with this line, "The cure is obviously NOT around the corner with HIV - nobody is anywhere near doing a study (itself a 2/3/4-year endeavour) with an expected outcome being the eradication of HIV"

Firstly many animals have something inside themselves that suppresses the virus completely, and they live and thrive with no problem. Scientists are very very close to mimicing that susbstance in human body for complete suppression of hiv virus. very very close. do a wikipedia search on herpes for example, there are 9 versions and 99% of people have 7 of them in their body and the body suppresses them completely just fine.

cats, hyenas, gorillas and monkey macaques they all completely supress virus naturally and that is exactly what science is trying to do and studying and working on every day for last 25 years, please read my posts about cd8 cells or other posts in research

if the virus is completely suppressed by the body I would call that a cure. like i said you and 99% of population have 7 or 9 herpes viruses in body ... 9% of entire human geneome are retroviruses that got stuck there in last 5 billion years of evolution

do you know

only one in one million cd4 cells even has the hiv virus in it, no mater what your VL and cd4 count is... say you have VL very high or med or low, still only about one in one million cd4 cell is even infected. and science just learned why a few months ago... it is called cd4 T cell homing, the immune system thinks the fight against the virus is over each day and sends a chemical signal to the cd4 cells to return to the node (even the ones that are not infected with hiv) and self distruct

when you say eradication of hiv... look you and all humans have 6 herpes viruses all thru your body but the body suppresses all of them every day, they are not active they are in the cells all over the body but suppressed... i call that eradicated.

There are eight distinct viruses in this family known to cause disease in humans. These viruses are (HHV stands for human herpesviruses): 3-8 are in over 90% and most cases 99% of humans, 1 and 2 are in 33% or more of humans...

B virus (Cercopithecine herpesvirus-1, herpesvirus simiae) is a simplexvirus endemic in macaque monkeys. Human zoonotic infection with this virus results in severe pathogenesis and often death in untreated individuals.

I am posting this to show that humans have viruses in their bodies and that the body can naturally suppress and to me that is a cure, suppression, science is very close to finding the suppressor vaccines, gene therapy, meds that stop hiv ... i am not talking about nukes, non nukes and protiease, i am talking about Nef, TAT, vue, inhibitors, and other new things...

http://www.herpes.org.uk/ George Kinghorn, GU consultant in Sheffield told us: "What I am suggesting to you is that to be infected with a herpes simplex virus is a state of normality. We tend to make this into a big deal instead of to say that to be infected with herpes virus is something that happens to all adults, some with symptoms and some of us without." Read the full text of Dr Kinghorn's talk

1 - Herpes simplex virus type 1 (short version - see also cold sores):How common? By age 15 around 25% of UK population, by age 30 around 50%. The rates are much higher in other countries.

2. Herpes simplex virus type 2 (short version - see also our Frequently asked questions):How common? Around 25% of the sexually active UK population. Over the whole country between 3% and 10%. The rates are much higher in other countries.What does it cause? Often nothing, at its most obvious it causes a flu-like illness followed by blisters or ulcers on the affected skin. If it recurs, there are likely to be fewer blisters.

3. Varicella-zoster virus (short version - see also our shingles and post-herpetic neuralgia pages):How common? Almost 100% of UK population by adulthood. However in tropical countries the rates are much lower.How is it caught? Chickenpox is caught like flu: virus floats in the air, from the breath of an infected person.What does it cause? A flu-like illness followed by blisters over the body. If it recurs, as shingles, the blisters will be a restricted area, often around the ribs. Older people may develop post-herpetic neuralgia, a pain the nerves that may be severe and may last for months or year. See our pages on how this is treated.

4. Epstein Barr virus (EBV, also called glandular fever, mononucleosis, mono, kissing disease):How common? Virtually everybody worldwide.How is it caught? Saliva.How long before it appears (incubation period)?What does it cause? In babies and children, the symptoms are often so mild that they are not noticed. In teenagers and adults it causes a fever, swollen glands, aching joints and it may cause ongoing fatigue. If it recurs, it will cause the same symptoms but they will not be as strong and will not last as long. People on drugs following organ transplants may suffer from ill-health caused by this virus. EBV may be in the news because it can sometimes cause a cancer called lymphoma. This cancer occurs in children with malaria in tropical countries and in adults in China.

5. Cytomegalovirus (CMV)How common? Half the population has CMV by a young age, with higher rates of infection in poorer areas.How is it caught? The virus is present in saliva, breast milk and other secretions.How long before it appears (incubation period)? ... to be completed ...What does it cause? In adults, it is usually caught with no symptoms at all. Sometimes it causes the same symptoms as a mild glandular fever (see above).

6. Human herpesvirus 6 (roseola infantum/exanthem subitum)How common? By the age of 2, almost all babies have type 6B virus.How is it caught? Saliva, and, in older people, possibly semen and other secretions.How long before it appears (incubation period)? 5 to 15 days.What does it cause? There are two types 6A and 6B. Type 6A has not been shown to cause any disease. Type 6B causes roseola in babies between 6 months and 1 year old. It is usually a mild infection, which is self-limiting. Symptoms include a fever lasting for a few days, swollen glands and normally a mild rash which appears after the fever goes. Occasionally children will have a swollen liver. Is is a major cause of fever induced seizures in babies. Since it is usually caught in childhood it is rare for adults to get this virus. If they do it is a more serious illness than in babies. HHV-6B has rarely been associated with a variety of viral illnesses, including mononucleosis syndromes, focal encephalitis, and pneumonitis.

7. Human herpesvirus 7:How common? By the age of 3, almost all children have HHV-7.How is it caught? Saliva, and, in older people, possibly semon and other secretions.What does it cause? Check back later when more information on this virus has been added to the website.

8. Human herpesvirus 8 (also called Karposi's sarcoma herpes virus or KSHV) How common? This virus is quite common in some parts of the world. In Europe and the US it is not very common - under 10% have it.Check back later when more information on this virus has been added to the website.How is it caught?How long before it appears (incubation period)?What does it cause?

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mistertonky

I agree 100% with Bimazeck.We can say that before hiv no virus had been really deeply studied and there were no really drugs against any virus.What does it means? that it is impossible for ever to find or to develope a drugs to eradicate the virus hidden in any cells?absolutely no.

This is an interesting poll. I would consider those that visit these forums to be more up on the news of HIV treatment and potential for vaccines and cures. Does it amaze anyone else that 51 of 104 respondents say that they think HIV/AIDS will be cured in the near future? I voted yes but not in the next 10 years, call me conservative I guess.

And the way the poll is constructed "near future" means in less than five years. I think 50% of the folks who voted are being a bit rosy in their assessment, either that or they really didn't read the choices well.

I agree 100% with Bimazeck.We can say that before hiv no virus had been really deeply studied and there were no really drugs against any virus.What does it means? that it is impossible for ever to find or to develope a drugs to eradicate the virus hidden in any cells?absolutely no.

i had read all of your texts. but i think HIV can be completely cured in 5 or 10 years. or at most 15 years. i know some of you may not agree with me.

but , guys, think somethings following,

1,now there are over 40 millions HIV POZ in the world. and HIV are still spread very rapidly. with this pace , may be we will have more than 100 million"fellows" in 5 to 10 years. and the population on the earth might raise to nearly 6.5 billion. so that means more than 1.5% population on the earth are HIV+. a basement of 1.5% of HIV+ population can make any one country kaput. guys, is there a country,which want to be destroyed?

2, whether earlier or today, the biggest group of POZ people are the youths, i mean the people between 15 to 30 years old. more than 40% of POZ people are in this age. and everyday over 2 million youths will be infected. the youths are the biggest labour force group in whole world. it can lnfluence the global economy very badly and deeply. is there a government, which want his ecomony to have a big red minus number?

3, except HIV, there are so many new viren had appeared on our planet. we even didn't know how it work after we just knew them. maybe there will be one virus that can destroy our human, and worse than HIV. we need to defeat HIV!

4, the hardest part to defeat HIV is the gene-mutation. but our scientists had just already found or begun to comletely discover the strutures of our human DNA, and it develops very quickly. and there would be endly a way to defeat HIV very soon in the future.

so, i don't think any government want his society and economy to be destroyed. and i believe we will be cured in a not very ong time.

what we need to do is just be ourselves and living happily and positive!

Especially considering that the family herpesviridae are DNA viruses and their genetic codes have all the stability that that implies.

Herpes viruses also appear to have something that's called the HHV Latency Associated Transcript. This essentially allows all bits of the herpes virus except the Latency parts to switch off when infecting humans. Think chicken pox. You get it... flare up with chicken pox... and this little thing is reproducing that part of its genome until some appropriate moment and then shingles!

We also, as has been pointed out, been living with herpes viruses possibly for hundreds of thousands of years, thus allowing a sort of parity through the beauties of natural selection between that particular virus family and the human immune system.

HIV, being an RNA virus, using reverse transcriptase to copy its viral RNA into DNA so our cells can make more of it. We all know this process is somewhat akin to allowing a drunken secretary take down dictaphone messages. There are a lot of mistakes that are going to be made. This is what allows HIV to mutate so fucking rapidly.

It's also been infecting humans only for about 50 years... which is absolutely no time on the scale of human evolution... so yes, it's possible that within 10,000 years, HIV could have all the seriousness of a herpes outbreak... but that doesn't help any of us.

However, given HIV's inherent weirdness, even for a retrovirus, the comparison to herpesviridae isn't warranted.

Not trying to put words in Bimazek's mouth, but I suspect that the point wasn't that HIV = herpes, but rather that most of us live with all sorts of critters inside us all the time. The implication is that these bacteria, viruses, etc. don't do us much harm because our bodies keep them in check and that perhaps a therapeutic vaccine or similar approach could enable our bodies to do the same to HIV. The existence of long-term non-progressors proves that the human body is physically capable of doing this, and the winning approach would extend this now-rare ability to most poz folk. The other message here (echoed several times in these forums) is that even if this treatment isn't a true cure (eradication), it'd presumably be "just as good" because it'd allow us to keep HIV in check, dump our meds, not be monitored (at least not as frequently), and be able to live our lives without giving much thought to HIV.

I'd like to say this is doable, and there's some exciting research in this area...anti-tat, dendritic cells, and so on. It's true that HIV research has hit many snags over the years, but there have also been surprising successes. If you'd mentioned the words "undetectable viral load" to someone, even a health care professional, 15 years ago, he/she might have laughed in your face and said "dream on." If you'd said "immune reconstruction" or "rising t-cells," they might have spit out the old lecture "hummankind has never faced a disease like...styming researchers...have to be realistic...back to square one."

So while I'm not saying break out the party hats and champagne/sparkling grape juice just yet, I do think there is good reason to have hope and to think that HAART will be surpassed by something much better-maybe not in the next couple of years, but in the not-too-distant future.

The existence of long-term non-progressors proves that the human body is physically capable of doing this, and the winning approach would extend this now-rare ability to most poz folk.

I'm not sure. I would tend to believe they are simply a genetic anomaly. What bimazek seems to allude to is a longer term evolutionary response in human's to a virus, and like Benj/aupoint points out that takes hundreds of thousands of years to occur naturally.

However, of course LTNP are useful in and only if we can unlock their unique genetic response and bottle it. I still think it's somewhat dangerous to make comparisons between regular viruses and a retrovirus. HIV is the first human one, or the 2nd and therefore we have zilch experience in dealing with one. Hence why I don't honestly believe something will happen in the next 5 years as reflected by 50% of the voting posters in the poll at the beginning of this thread. It's simply way beyond the rosiest of scenarios that I can imagine.

i agree with the two posts two above this one supporting bimazek, me, and i disagree with -- aupointillimite because, 9% of the entire human genome is retro viruses that somehow got lodged in our dna and dealt with over last 200 million years of evolution, so retro or not retro have been dealt with for a long time...

cd8s are the way naturally the body of all animals that get a version of hiv suppress... for example cats, gorillas, hyenas, mycacs, etc...if you are with a research study or a univ. or a md who is very very advanced...print this http://forums.poz.com/index.php?topic=7475.0aboutcd8s and ask him about it

I read that all vaccine trials done in past have to be repeated because as long as CD8s get signal (is it a protein?) to shut off and not fight off the hiv virus the vaccine will fail because of cd8s no mater how good the vaccine is...

there is a med, called

anti-pd-1 also anti-ctla which are monoclonal antibodies that if given with a vaccine or med would have totally different results...

at least that is how i read this science

or one about homing signals... do a search for homing by author bimazek

Although combination therapy allows suppression of HIV-1 viremia to undetectable levels, eradication has not been achieved because the virus persists in cellular reservoirs, particularly the latent reservoir in resting CD4+ T lymphocytes. We previously established an SIV/macaque model to study latency. We describe here a novel mechanism for the induction of SIV from latently infected resting CD4+ T cells. Several human cell lines including CEMx174 and EBV-transformed human B-lymphoblastoid cell lines mediated contact-dependent activation of resting macaque T cells and induction of latent SIV. Antibody blocking assays showed that interactions between the co-stimulatory molecule CD2 and its ligand, CD58, were involved whereas soluble factors and interactions between T cell receptors and major histocompatibility complex class II were not. Combinations of specific antibodies to CD2 also induced T cell activation and virus induction in human resting CD4+ T cells carrying latent HIV-1. This is the first demonstration that co-stimulatory signals can induce latent virus without co-engagement of the T cell receptor, and this study might provide insights into potential pathways to target latent HIV-1.

I'd like to drop a line or two, to those of you who are on this thread. I've read all your banter, both negative and positive as to a cure. I do have hope, but I believe that the day there is a cure, we must all prepare ourselves for the rapture, shortly there after. Peace in the middleeast, will probably coincide with this development, and all our joy will be short lived. Hope you all have made amends.

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mistertonky

Year Began Improvement Plan Status Comments 2004 Adopt the revised goal of extending the timeline for developing an AIDS vaccine from 2007 to 2010, to more realistically reflect the state of the science. Completed Completed in 2004 2005 Expand breeding of non-human primates at 3 Centers by 2005. Completed Long-term Goal: By 2010, develop an HIV/AIDS vaccine. Achieved: Breeding expanded to 3 Centers. 2005 Develop 3 anti-HIV compounds by 2005. Completed Long-term Goal: By 2007, evaluate the efficacy of 3 new treatments. Achieved: Developed 3 anti-HIV compounds. 2006 Initiate 1 new Phase IIb trial to determine if a third generation vaccine candidate has efficacy. Completed Long-term Goal: By 2010, develop an HIV/AIDS vaccine. 2006 Evaluate interventions to reduce mother-to-child transmission of HIV and assess the impact of these interventions on future treatment options for women and children. Completed Long-term Goal: By 2007, evaluate the efficacy of 3 new treatments. 2007 Initiate another Phase II/IIb trial(s) of the most promising third generation vaccine candidate. Action taken, but not completed Long-term Goal: By 2010, develop an HIV/AIDS vaccine. 2007 Achieve goal of evaluating the efficacy of three new treatment strategies for HIV infection in clinical trials in an effort to identify agents or combinations of agents that are more effective, less toxic, and/or simpler to use than the current recommended HIV treatment regimens. Action taken, but not completed Long-term Goal: By 2007, evaluate the efficacy of 3 new treatments. 2008 Initiate a Phase IIb trial of a promising vaccine candidate that may protect across viral clades (or subtypes). Action taken, but not completed 2008 Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of expiring grants to determine reallocation of resources for priority research. Action taken, but not completed Efficiency Measure: By 2010, utilize enhanced ARIS database to more efficiently conduct portfolio analysis to invest in priority AIDS research

Explanation:Complications are emerging from the current HAART therapy regimen so there is an urgent need for the discovery and development of new drugs that are less toxic, simpler to use, and affordable.

I'd like to drop a line or two, to those of you who are on this thread. I've read all your banter, both negative and positive as to a cure. I do have hope, but I believe that the day there is a cure, we must all prepare ourselves for the rapture, shortly there after. Peace in the middleeast, will probably coincide with this development, and all our joy will be short lived. Hope you all have made amends.

Finally, a perspective we can all agree with. Discomfort to Zion! Eat the rich!

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"Many people, especially in the gay community, turn to oral sex as a safer alternative in the age of AIDS. And with HIV rates rising, people need to remember that oral sex is safer sex. It's a reasonable alternative."

I doubt .Because of the following :1.The prevalent opppinion is that " nowadays medicine keep our illness under tolerable control " and that "HIV/AIDS has become a light chronicall illness ". I think that these opinions are launched by big pharmaceuticals .They do not wanna find vaccine or a true medicine until they spent all their old medicine supplies.2.A virus is hidden in a place ( brain and nerve cells ) which are unreachable to a modern medicine

I think that our only hope is a vaccine of somekind and that it would be found by small companies ( with a lot of luck to pass big predator companies )

it is a well known story that there were a few people who has found a reallyrevolutionary things like washing machine which use no w.powder and a long life airplane tyres ..................Guess what happened next.......They were visited by the big companies representatives and offered a blank check to put their innovations into a ground. Al

mistertonky

The business regard the "cure" will be a huge business ( vaccine or drugs... i dont care)The big pharma like so much the money eh eh.even the small company loves the money.The hiv virus is not hidden in the brain cells.. is hidden in the macrophagy in the blood inside the brain... it is different.

When we were children we dreamed wonderful things, believed in Fairies and Father Christmas and the magic and the miracles.Let us believe that Yes there will be a cure that can make life easier, a life that is longer than we initailly thought, that life is worth living. that we love life. and that we love our lives, and that we love others who love us.

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'I see your heartache, your eyes say it all, will always be there for you!' mum

mistertonky

HIV initially enters the brain by passage of HIV-infected cells from the blood.

Since HIV does not infect neurons, it is unlikely that direct viral replication within these cells accounts for their loss. However, viral proteins may play a part in neuronal cytotoxicity since gp120 and Tat protein have been shown to be toxic for neurons in culture (for review, see Geleziunas et al. 1992; Levy 1993). The effects of gp120 on neuronal cell growth might be due to its ability to bind to receptors for neuronal growth factors, since some sequence similarity exists between a portion of gp120 and both neuroleukin and vasoactive intestinal peptide. The significance of these similarities awaits experimental testing.

Nerve cells are not directly infected by HIV, suggesting that nerve cell death is a response to toxic factors released from the virus itself or by neighboring cells. Several potential candidates for the AIDS dementia neurotoxin(s) have been identified, but it remains uncertain which factor is the true culprit.

herpes retrovirus infect nerve cells... it is much different than hiv retrovirus.

The biggest problem is to flusghing out or activate the very very small number of resting cd4.

The scientisti know so much about the latency, that it is not possible to believe they can not eradicate a small number of infected cd4.

I'm not sure why this thread went all Herpes for a while. None of these viruses have much similarity with HIV. I understand the point made about us all have bugs inside us that we suppress, as some species of monkeys do with SIV, but the monkeys took a while to evolve to that point and I don't fancy waiting. Some species of monkey are still badly affected by SIV.

The fact remains that there are, to my knowledge, no treatments currently being trialled as a prospective cure for HIV. This means more than 5 years until a possible cure at least, no matter how good the basic science looks. There are some promising approaches that have been tried in mice and in cell culture, but it takes 5-10 years to get this stuff anywhere near a patient. And so far, basic science cannot figure out a way to sort out latency or viral reservoirs.

For me, controlling HIV in the blood even w/o meds isn't cure. Cure is eradication.

The term you are looking for is "Sustained Virological Response" meaning the virus doesn't come back off meds ever. There will always be the guts of inactive HIV in the blood and HIV antibodies. But the body would have no active HIV. That's as good as it would get.

R

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.